P1185: ANTITUMOR ACTIVITY AND SAFETY OF ZANUBRUTINIB COMBINED WITH R-CHOP REGIMEN IN THE TREATMENT OF NEWLY DIAGNOSED NON-GCB DLBCL WITH EXTRANODAL INVOLVEMENT: A PROSPECTIVE PHASE II STUDY.
Authors: C. Li, H. Geng, X. Zong, J. Zhou, Y. Zhang, J. Li, S. Jia, D. Wu
Journal: HemaSphere (2022)

Background: Approximately one-third of Diffuse large B-cell lymphoma(DLBCL) arises primarily from extranodal sites,less than 70% showed extranodal involvement in at least 1 site.Patients with multiple extranodal involvement indicates adverse clinical outcomes,and non-GCB subtype is another poor prognostic factor.Study shows that the rates of complete remission(CR),five-year OS,five-year PFS were significantly lower for the non-GCB subtype(77.5% vs 52.6%,78% vs 54%,76% vs 48%).Patients who failed in initial treatment had poor prognosis and short overall survival.In the genetic taxonomy, with non-GCB tumors enriched for MCD and BN2 subtype are suitable for the treatment of BTK inhibitor.Zanubrutinib has shown very promising future in newly diagnosed and relapsed/refractory B-cell lymphoma. Aims: We conducted a single-arm,phase II trial for newly diagnosed non-GCB DLBCL with extranodal involvement to evaluate the efficacy and safety of the zanubrutinib combined with R-CHOP(number NCT 04835870). Methods: 20 patients enrolled in this prospective single-center study with newly diagnosed non-GCB DLBCL from October 2020 to February 2022.Patients received therapies:R-CHOP(intravenously rituximab(375mg/m2 on Day0), cyclophosphamide(750mg/m2on Day1),doxorubicin(50mg/m2 on Day1),vincristine(1.4mg/m2 on Day1),and oral prednisone(50mg/day Day1-5) with Zanubrutinib(160mg bis in die orally) regimen. Particularly,patients with a weak constitution or older than 70 years old were administered ZR-miniCHOP. Results: 20 patients received ZR-CHOP regimen treatments, Patients had a median age of 60 years(31~83years) and 4 patients were over 70 years old,11 patients (55%) had IPI-PS ≥3 score,16 patients (80%) had stage III/IV disease,13 patients (65%) had ≥2 extranodal organs involved,2 patients (10%) had bulky disease and 9 patients (45%) were double-expression lymphoma confirmed by immunohistochemistry and FISH (Table 1). The median follow-up time of all patients was 8.7 months(0.4~16.1months) and there are 12 patients received 6 ~ 8 cycles of treatment who can evaluate the efficacy. The objective response rate(ORR) of 12 patients was 91.67%(11/12),11 patients(91.67%) reached complete remission(CR),of which 9 achieved CR at the interim evaluation, and 1 patient(8.3%) reached progression disease(PD).The median OS and PFS of the 12 patients who finished treatment were 10.7months(5.6~16.1months) and 10.2months(5.6~16.1months).One patient relapsed(Figure 1).13(65%) patients reduced the dose during treatment, the most common AEs were hematological toxicity, fatigue and apositia. all-grade and grade 3 or higher hematological toxicity were 100% and 65%,11 patient observed grade 3 or higher neutropenia and 3 patients had severe pneumonia during treatment. Hemorrhage were observed in 3 patients,2 patients developed atrial fibrillation after the first medication.No patient had fatal adverse events(Table2). Image:Summary/Conclusion: Our results showed that Zanubrutinib plus R-CHOP(ZR-CHOP) is a safe and effective scheme for this part of non-GCB DLBCL patients with extranodal involvement.It indicate that the addition of zanubrutinib to the standard first-line treatment can enable these patients to achieve remission in the early stage of treatment and without significantly increasing toxicity.